No Negative Neurodevelopmental Issues With Late Exposure to Antenatal Steroids

— Follow-up to ALPS trial offers reassuring results for late preterm corticosteroids

by
Ed Susman, Contributing Writer, MedPage Today
February 12, 2023

SAN FRANCISCO – Giving late preterm antenatal corticosteroids did not impact childhood neurodevelopmental outcomes, a researcher reported.

In a follow-up to the ALPS study, there were no statistically significant differences in the scores of children exposed to corticosteroids or to placebo in the third trimester based on cognitive testing, according to Cynthia Gyamfi-Bannerman, MD, of the University of California San Diego.

Testing in the study was done by a certified psychologist using the second edition of the Differential Ability Scales (DAS-II) core components of general conceptual ability, and included verbal reasoning, non-verbal reasoning, and spatial ability, Gyamfi-Bannerman explained in a presentation at the Society for Maternal-Fetal Medicine meeting.

Among children who were exposed in utero to betamethasone, 17.1% scored <85 (one standard deviation below the mean) on the test while 18.5% on placebo scored <85 (adjusted RR 0.94, 95% CI 0.73, 1.22), she said.

The researchers also found no significant differences between the two study groups for various secondary outcomes.

“This was the largest follow-up study of late preterm steroids and one of the largest follow-up studies of antenatal corticosteroids,” Gyamfi-Bannerman said.

The 2016 ALPS study by Gyamfi-Bannerman and colleagues was done with women with a singleton pregnancy at 34 weeks/0 days to 36 weeks/5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks/6 days). One of the findings was that neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs 15.0%).

“Prolonged and persistent hypoglycemia has been associated with adverse neurodevelopment in preterm infants,” Gyamfi-Bannerman noted.

The current study was a prospective follow-up of the mothers in the ALPS at one of 13 centers that participated in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Mothers who consented to future contact were eligible if their child was at least age 6 years. Those enrolled in the follow-up study were age 29 and the majority were white with private health insurance.

The researchers reported that, of 2,831 children from ALPS, 1,026 were enrolled and 949 completed the DAS-II. There were 479 children exposed to betamethasone and 470 in the placebo group. Maternal and neonatal characteristics were similar between groups aside from neonatal hypoglycemia, which was more common in the betamethasone-exposed children (29.9% vs 18.8% for placebo), Gyamfi-Bannerman said.

For secondary outcomes, the researchers reported the following for betamethasone versus placebo:

• Gross Motor Function System Classification score level >1: 0.2% vs 0.2%
• Social Responsiveness Scale >65: 13.5% vs 14.3% (adjusted RR 0.92, 95% CI 0.60, 1.24)
• Child Behavior Checklist total problems t-score: 48.5 vs 49.1 (adjusted RR -0.81, 95% CI -2.15, 0.52)

Study limitations included the fact that the planned sample size was 2,000, and the follow-up enrolled slightly over half that number as the “COVID pandemic severely affected our ability to enroll,” the researchers explained. Still, based on the study sample of 949 participants, “we are 95% confident that our true point estimate is between 0.73 and 1.22,” they stated.

Christina A. Penfield, MD, MPH, of NYU Langone Health in New York City, called the study findings “reassuring because there has been lingering concern about the long-term consequences of steroid administration [in this population].”

But Penfield, who was not involved in the study, cautioned that “I would still like to see the full results with the subgroup analyses from this follow-up study, especially for the children who had neonatal hypoglycemia.”

Jamie Lo, MD, of the Oregon Health Sciences University in Portland, told MedPage Today, that “this information is very useful when counseling patients at risk for late preterm birth as there was no prior safety data regarding longer-term childhood outcomes.”

“The literature on repeated chronic steroid administration has demonstrated an adverse impact on offspring neurodevelopment and function, but there was no existing data on the neurodevelopmental outcomes from the two corticosteroid doses in the late preterm gestation as administered in the ALPS study. This study now fills this gap in knowledge regarding the longer-term safety profile of late preterm steroids,” added Lo, who was not involved in the study.